Embryonic or fetal specific, surface antigen determinants (EAs) are expressed on developing embryos and fetuses in inbred, syngeneically mated rodents (hamster, mouse, rat, guinea pig). Studies in this laboratory and from elsewhere have documented that the pregnant mother produces both antibody and apparent thymus (T) dependent cell mediated immune responses to EAs during gestation. The regulation of the quality and quantity of this maternal immune response to EAs is only sketchily understood but most pregnancies proceed to term with the delivery of healthy issue in the face of maternal cytostatic IgG and cytotoxic lymphocytes in certain tissues which can be detected against EA bearing target cells. Oncofetal determinants (OFAs), very similar if not identical to EAs, appear on most major rodent and human tumor types tested. OFAs, like EAs, are immunogenic to the tumor-bearing host during early oncogenesis by viruses and chemical carcinogens and yet the tumors grow and kill the host. The aim of this project is to fully characterize the immunoregulatory control exacted in pregnant mice and hamsters against specific, biochemically characterized EAs we have detected in the mouse and hamster fetus. These selected EA determinants are demonstrated to be immunogenic to the pregnant female eliciting both IgG and apparent T-lymphocyte mediated immune responses which are regulated by unknown mechanisms. Contemporary in vitro and in vivo immunologic techniques and lymphocyte-typing reagents will be used to characterize the functional interactions of helper, cytotoxic, suppressor and contrasuppressor lymphocyte activities in the course of syngeneic pregnancy in BALB/c mice and, later in LSH hamsters. Several purified EAs, recently prepared in this lab, will be used for critical in vitro analyses to establish the specific determinants involved in regulatory interactions detected. In the last years of the project, a parallel analysis of key components described in immune regulation characterized in the pregnant mice in the initial phase of the study will be assessed in mice undergoing primary chemical carcinogenesis and in hamsters undergoing viral carcinogenesis.